The present invention concerns a process for preparing 3-cyano-8-substituted-8-azabicyclo[3.2.1]octanes. 3-Cyano-8-substituted-8-azabicyclo[3.2.1]octanes are useful as intermediates for certain insecticides (see, for example, WO 96/37494).
The present invention provides a process for the preparation of a compound of formula (I): 
the process comprising the steps:
i. adding a solution of a compound of formula (II): 
xe2x80x83in aqueous hydrochloric acid to an aqueous solution of sodium cyanide at a temperature in the range xe2x88x925 to 10xc2x0 C.; and,
ii. mixing the resulting mixture at a pH in the range 8.5-9.5 and a temperature in the range xe2x88x925 to 5xc2x0 C. for 15-24 hours under efficient agitation conditions, the concentration of sodium cyanide in the resulting mixture being greater than 2.4 molar.
The solution of the compound of formula (II) in step (i) is preferably prepared by dissolving the compound of formula (II) in concentrated (about 36%w/w) hydrochloric acid and then adding an appropriate amount of cold water (preferably below 5xc2x0 C.).
During Step (ii) the initial reaction mixture of a precipitate of compound (II) and compound (I) and the endo-cyano epimer of compound (I) is slowly converted to compound (I). In order to promote this two-phase reaction efficient agitation conditions sufficient to break the particles forming the solid phase (preferably high-shear conditions to enable a greater degree of particle breakage) are required. Such agitation conditions are fully described in Chapter 6 of xe2x80x9cMixingxe2x80x94principles and applicationxe2x80x9d by S. Nagata, John Wiley 1975.
In one aspect the present invention provides a process as hereinbefore described wherein the pH range in step (ii) is 9.0-9.3.
In another aspect the present invention provides a process as hereinbefore described wherein, in step (ii), the concentration of sodium cyanide in the resulting mixture is greater than 3.5 molar.
In a further aspect the present invention provides a process as hereinbefore described wherein the agitation conditions of step (ii) are sufficient to break the particles of a precipitate forming a solid phase. In a still further aspect the present invention provides a process as hereinbefore describedwherein the agitation conditions are high-shear conditions.
In another aspect the present invention provides a process as hereinbefore described wherein step (ii) is conducted at a temperature in the range 0-2xc2x0 C.
In a further aspect the present invention provides a process for the preparation of a compound of formula (I) comprising the steps:
i. adding a solution of a compound of formula (II) in aqueous hydrochloric acid to an aqueous solution of sodium cyanide at a temperature in the range xe2x88x925 to 10xc2x0 C. (preferably about 0xc2x0 C.); and,
ii. mixing the resulting mixture at a pH in the range 8.5-9.5 (preferably 9.0-9.3) and a temperature in the range xe2x88x925 to 5xc2x0 C. (preferably about 0-2xc2x0 C.) for 15-24 hours (preferably 17-20 hours) under efficient agitation conditions, the concentration of sodium cyanide in the resulting mixture being greater than 2.4 molar (preferably greater than 3.5 molar). In the following Examples, Examples 1 to 3 illustrate the invention.